7. Project Summary Drug-related overdose deaths are now the largest cause of injury death in the United States, having eclipsed motor vehicle-related deaths in 2011. Evidence suggests that individuals initiating prescription opioid abuse within the last 10 years are demographically different from opioid abusers of previous generations. They are more rural and suburban than urban, and have a broader range of age of initiation. Previous studies of transition from non-injecting to injecting drug use has largely been conducted in highly urban environments, and studies of HIV risk behaviors among injecting drug users in the United States have also predominantly been conducted in urban settings. Surprisingly little is known about prescription opioid users in suburban and exurban settings, or about factors associated with transition from prescription opioid use or misuse to injecting or to use of heroin. Southern California has three counties largely comprised of suburban/exurban and rural communities, high rates of HIV, and limited services for people who inject drugs: Ventura, Orange, and San Diego Counties. These three counties have higher than state median rates of prescription opioid prescribing, and higher than state median rates of accidental opioid-related overdose death. We propose to utilize our unique access to a large population of suburban and exurban drug users to recruit individuals who are using prescription opioids not as prescribed, or who have recently (<6 months) transitioned to injecting opioids and/or heroin use, in order to conduct qualitative and quantitative exploration of a) initiation of prescription opioids, b) factors associated with transition to injecting and/or heroin use, and c) barriers to accessing medication assisted treatment, HIV and HCV testing, overdose prevention, and clean needles. We will achieve these aims through a three-stage mixed methods approach. We will use qualitative approaches to determine factors associated with initiation of opioid misuse, as well as transition to injecting, and/or transition to heroin use; quantitative surveys and analysis to determine statistical relationships between predictor factors and outcomes in a larger sample of prescription opioid misusers; and qualitative interviews to reconcile first-stage qualitative findings with quantitative findings. Findings from this study will be uniquely valuable in designing targeted interventions for preventing opioid pain reliever misuse, heroin initiation, injection initiation and overdose among high risk populations in geographically dispersed suburban and exurban communities, a group that to day has been the subject of little research.